| First Author | Tian J | Year | 1994 |
| Journal | J Exp Med | Volume | 180 |
| Issue | 5 | Pages | 1979-84 |
| PubMed ID | 7964474 | Mgi Jnum | J:21133 |
| Mgi Id | MGI:69174 | Doi | 10.1084/jem.180.5.1979 |
| Citation | Tian J, et al. (1994) T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J Exp Med 180(5):1979-84 |
| abstractText | Limited regions of amino acid sequence similarity frequently occur between microbial antigens and host proteins. It has been widely anticipated that during infection such sequence similarities could induce cross-reactive T cell responses, thereby initiating T cell-mediated autoimmune disease. However, the nature of major histocompatibility complex (MHC)-restricted antigen presentation confers a number of constraints that should make this type of T cell cross-reactivity a rare, MHC allele-dependent event. We tested this prediction using two insulin-dependent diabetes mellitus (IDDM)-associated antigens, coxsackievirus P2-C (Cox P2-C) protein and glutamate decarboxylase (GAD65), which share a prototypic sequence similarity of six consecutive amino acids within otherwise unrelated proteins. We surveyed a panel of 10 murine MHC class II alleles that encompass the spectrum of standard alleles for the ability to cross-reactively present Cox P2-C and GAD65. Out of the 10 restriction elements tested, the sequence similarity regions were both dominant determinants and were cross-reactively displayed after the natural processing of whole antigens, only in the context of I-Anod. These data show that cross-reactive T cell recognition of sequence similarity regions in unrelated proteins is confined to certain MHC alleles, which may explain MHC association with autoimmune disease. It is striking that these two diabetes-associated antigens were cross-reactively recognized only in the context of a diabetes susceptibility allele. Since the human and the murine class II alleles associated with IDDM share conserved features, cross-reactive T cell recognition of GAD65 and Cox P2-C may contribute to the pathogenesis of human IDDM and account for the epidemiological association of coxsackievirus with IDDM. |
